1. Field of the Invention
This invention relates to radiodiagnostic reagents and, more particularly, to polypeptides useful for producing technetium (Tc-99m) labeled radiodiagnostic agents. The invention relates to Tc-99m labeled reagents, kits for making such reagents, and methods for using such reagents.
2. Description of the Prior Art
U.S. Pat. No. 4,861,869 (Nicolotti) describes coupling agents of the formula: ##STR1## wherein R.sub.2 and R.sub.3 are the same or different and each represents a radical selected from the group consisting of alkyls having from 1 to 6 carbon atoms, aryls having from 6 to 8 carbon atoms and aklaryls having 7 to 9 carbon atoms, any of which can be substituted with one or more hydroxyl, alkoxy, carboxy or sulfonate groups; n is either 1 or 2; and X is an activating group capable of forming an amide bond with an alpha or beta amino group of a biologically useful protein or polypeptide molecule.
U.S. Pat. No. 4,861,869 also describes compounds such as S-benzoylmercaptoacetylglyclglyclglycine.
The coupling agents are bound to large peptides such as antibodies or fragments thereof and complexed to Tc-99m.
U.S. Pat. Nos. 4,571,430, 4,575,556 and 4,434,151 (Byrne et al.) describe compounds of the formula: ##STR2## wherein R is hydrogen or lower alkyl, R.sub.1 and R.sub.2 are individually hydrogen or lower alkyl or taken together form oxo; R.sub.3 is an amino protecting group where R.sub.1 and R.sub.2 taken together form oxo; R.sub.4 is hydrogen or lower alkyl; R.sub.5 is hydrogen or a thiol protecting group; and y and z are integers from 0 to 2; which are bifunctional chelating agents and as such can couple radionuclides to terminal amino-eontaining compounds capable of localizing in an organ or tissue which is desired to be imaged.
Bryson et al., Inorg. Chem. 27:2154-2161 (1988) and Inorg. Chem. 29:2948-2951 (1990), describes thiolate ligands for complexing with technetium of the formula: ##STR3## European Patent Application No. 86100360.6, filed Jan. 13, 1986, describes dithio, diamino, or diamidocarboylic acids or amine complexes useful for making technetium imaging agents.
Other references of interest include Khaw et al., J. Nucl. Med. 23:1011 (1982); Rhodes, B. A., Sem. Nucl. Med. 4:281 (1974); Davidson et al., Inorg. Chem. 20:1629 (1981); and Byrne and Tolman, J. Nucl. Med. 24:126 (1983). See particularly Fritzberg et al., J. Nucl. Med. 23:592 (1982); Fritzberg et al., ibid. 23:17 (1982), for descriptions of mercaptoacetyl derivatives of ethylene diamine carboxylic acid derivates. See also U.S. Pat. Nos. 4,434,151, 4,444,690 and 4,472,509.
European Patent Application 88104755.9 describes various S-protected mercaptoacetylglycylglycine chelating groups bound to large proteins such as antibodies.
European Patent Application 84109831.2 describes technetium complexes of compounds of the formula I and lI: ##STR4## wherein R and R.sub.6 are each selected from hydrogen, substituted or unsubstituted lower alkyl or --COR where R.sub.9 is selected from hydroxy, substituted or unsubstituted lower alkoxy, substituted or unsubstituted amino, glycine ester, or an activated leaving group; R.sub.1 is selected from hydrogen, or substituted or unsubstituted lower alkyl; R.sub.2 and R.sub.3 are each selected from hydrogen or a thiol protecting group; and R.sub.4, R.sub.5, R.sub.7, and R.sub.8 are each selected from hydrogen or lower alkyl; and salts thereof. These complexes were used primarily as renal function monitoring agents.
Arginylglycylaspartate (Arg-Gly-Asp or RGD) and derivative peptides are known to bind to blood clots (see U.S. Pat. Nos. 4,792,525, 4,857,508 and 4,578,079) and RGD derivatives have been labeled with technetium as imaging agents, Journal of Nuclear Medicine 31, pp. 757, No. 209 (1990).